Glucocorticoid receptor antagonists: new tools to investigate disorders characterized by cortisol hypersecretion

Increased cortisol levels have been observed in patients suffering from a number of metabolic and psychiatric disorders. In some of these disorders a causal relationship has been suggested between the increased cortisol secretion and the observed clinical phenomena. Glucocorticoid receptor antagonists which block cortisol effects might have a benefit in both the diagnosis and treatment of these disorders. Selective glucocorticoid receptor antagonists with in vivo potency have not been described thus far, partly due to the similarity between the glucocorticoid and progesterone receptors. In the present studies, we report on three different chemical classes derived from the glucocorticoid/progestagen antagonist RU486. Selected compounds from the classes 11-monoaryl steroids, 11,21-bisaryl steroids and 11-aryl, 16-hydroxy steroids proved to be selective glucocorticoid receptor binders with in vivo antagonistic activity. Most compounds were able to pass the blood-brain barrier. These compounds offer the opportunity to investigate and possibly treat patients with a disturbed hypothalamus-pituitary-adrenal axis without side effects caused by an antiprogestagenic action.     

Phenomenal characteristics associated with projecting oneself back into the past and forward into the future: influence of valence and temporal distance

As humans, we frequently engage in mental time travel, reliving past experiences and imagining possible future events. This study examined whether similar factors affect the subjective experience associated with remembering the past and imagining the future. Participants mentally "re-experienced" or "pre-experienced" positive and negative events that differed in their temporal distance from the present (close versus distant), and then rated the phenomenal characteristics (i.e., sensorial, contextual, and emotional details) associated with their representations. For both past and future, representations of positive events were associated with a greater feeling of re-experiencing (or pre-experiencing) than representations of negative events. In addition, representations of temporally close events (both past and future) contained more sensorial and contextual details, and generated a stronger feeling of re-experiencing (or pre-experiencing) than representations of temporally distant events. It is suggested that the way we both remember our past and imagine our future is constrained by our current goals.     

The redundant target effect is affected by modality switch costs

When participants have to respond to stimuli of two modalities, faster reaction times are observed for simultaneous, bimodal events than for unimodal events (the redundant target effect [RTE]). This finding has been interpreted as reflecting processing gains for bimodal relative to unimodal stimuli, possibly due to multisensory interactions. In random stimulus sequences, reaction times are slower when the stimulus is preceded by a stimulus of a different modality (modality switch effect [MSE]). Simple reaction time redundant target experiments with auditory-visual, visual-tactile, and auditory-tactile stimulus combinations were run to determine whether the RTE may be partly explained by MSEs because bimodal stimuli do not require a modality switch. In all three modality pairings, significant MSEs and RTEs were observed. However, the RTE was still significant after reaction times were corrected for the MSE, supporting the hypothesis that coactivation occurs independently of modality switch costs.     

A heart rate analysis of developmental change in feedback processing and rule shifting from childhood to early adulthood

Over the course of development, the ability to switch between different tasks on the basis of feedback cues increases profoundly, but the role of performance monitoring remains unclear. Heart rate indexes can provide critical information about how individuals monitor feedback cues indicating that performance should be adjusted. In this study, children of three age groups (8-10, 12-14, and 16-18 years) performed a rule change task in which sorting rules needed to be detected following positive or negative feedback. The number of perseverative errors was lower for 16- to 18-year-olds than for 8- to 10-year-olds, and 12- to 14-year-olds performed at an intermediate level. Consistent with previous findings, heart rate slowed following feedback indicating a rule change, and the magnitude of slowing was similar for all age groups. Thus, 8- to 10-year-olds are already able to analyze feedback cues. In contrast, 12- to 14-year-olds and 16- to 18-year-olds, but not 8- to 10-year-olds, showed heart rate slowing following performance errors, suggesting that with age children are increasingly able to monitor their performance online. Performance monitoring may therefore be an important contributor to set-shifting ability.     

The self salience model of other-to-self effects: integrating principles of self-enhancement, complementarity, and imitation

In a series of studies the Self Salience Model of other-to-self effects is tested. This model posits that self-construal salience is an important determinant of whether other-to-self effects follow the principles of self-enhancement, imitation, or complementarity. Participants imagined interactions (Studies 1 and 2) or were confronted (Studies 3 to 5) with dominant, submissive, agreeable, or quarrelsome person targets. Findings support the prediction that subsequent self-evaluations (Studies 1 to 3) and behaviors (Studies 4 and 5) follow the principles of self-enhancement when the personal self is activated (contrast away from undesirable targets, assimilation toward desirable targets); the principles of complementarity when the relational self is activated (contrast on the dominant-submissive dimension, assimilation on the agreeable-quarrelsome dimension); and the principles of imitation when the collective self is activated (assimilation regardless of desirability or dimension).     

The relationship between the Big Five personality factors and burnout: a study among volunteer counselors

In the present study of 80 volunteer counselors who cared for terminally ill patients, the authors examined the relationship between burnout as measured by the Maslach Burnout Inventory (C. Maslach, S. E. Jackson, & M. P. Leiter, 1996) and the 5 basic (Big Five) personality factors (A. A. J. Hendriks, 1997): extraversion, agreeableness, conscientiousness, emotional stability, and intellect/autonomy. The results of 3 separate stepwise multiple regression analyses showed that (a) emotional exhaustion is uniquely predicted by emotional stability; (b) depersonalization is predicted by emotional stability, extraversion, and intellect/autonomy; and (c) personal accomplishment is predicted by extraversion and emotional stability. In addition, some of the basic personality factors moderated the relationship between relative number of negative experiences and burnout, suggesting that personality may help to protect against known risks of developing burnout in volunteer human service work.     

The use of recognition information and additional cues in inferences from memory

Goldstein and Gigerenzer's (2002) "Recognition Heuristic" (RH) was tested for its empirical validity in an experimental paradigm with induced recognition of objects. RH claims that upon inferring which of two objects (e.g., cities) scores higher on a criterion (e.g., city size), a recognized object will be chosen over an unrecognized one, if the recognition is a valid predictor of the criterion without considering additional object information. Trying to avoid potential shortcomings of former studies, we (a) used the city population task, (b) provided additional cue information only for recognized cities, and (c) had participants draw inferences from memory. Participants learned city names and additional information about some cities. They also learned that recognition and the additional information were valid predictors of the criterion "city size". In a subsequent decision phase, the additional information about the cities in memory strongly affected the inferences, suggesting that recognition information is clearly integrated into judgments, but by no means in a non-compensatory fashion that would dominate every other cue.     

The association between parenting stress, depressed mood and informant agreement in ADHD and ODD

OBJECTIVE: In Attention Deficit Hyperactivity Disorder (ADHD) agreement between parents and teachers is often low. Parental depressed mood and parenting stress are considered to decrease informant agreement. This study examined informant agreement in children with ADHD and the association between parental depressed mood, parenting stress and agreement in the ratings of ADHD, ODD and CD symptoms. METHOD: 65 parents completed questionnaires on ADHD behavior of their child, parenting stress and depressed mood, teachers reported on ADHD behavior. RESULTS: Low agreement was found for hyperactive and moderate agreement for inattentive, ODD and CD symptoms. Stepwise regression analyses showed that parenting stress, and not parental depressed mood accounted for 12% of the variance in inattention symptoms disagreement, 14% of the variance in hyperactive symptoms disagreement and 9% in oppositional behavior disagreement. No significant predictors were found for CD disagreement. The found effect was independent of stimulant medication use. CONCLUSION: Parenting stress, but not parental depressed mood, was associated with the disagreement between parents and teachers on both ADHD and ODD symptoms. These results emphasize the importance of considering parenting stress in diagnosing ADHD and comorbid ODD.     

A dynamical model of general intelligence: the positive manifold of intelligence by mutualism

Scores on cognitive tasks used in intelligence tests correlate positively with each other, that is, they display a positive manifold of correlations. The positive manifold is often explained by positing a dominant latent variable, the g factor, associated with a single quantitative cognitive or biological process or capacity. In this article, a new explanation of the positive manifold based on a dynamical model is proposed, in which reciprocal causation or mutualism plays a central role. It is shown that the positive manifold emerges purely by positive beneficial interactions between cognitive processes during development. A single underlying g factor plays no role in the model. The model offers explanations of important findings in intelligence research, such as the hierarchical factor structure of intelligence, the low predictability of intelligence from early childhood performance, the integration/differentiation effect, the increase in heritability of g, and the Jensen effect, and is consistent with current explanations of the Flynn effect.     

The beat goes on: rhythmic modulation of cortical potentials by imagined tapping

A frequency analysis was used to tag cortical activity from imagined rhythmic movements. Participants synchronized overt and imagined taps with brief visual stimuli presented at a constant rate, alternating between left and right index fingers. Brain potentials were recorded from across the scalp and topographic maps made of their power at the alternation frequency between left and right taps. Two prominent power foci occurred in each hemisphere for both overt and imagined taps, one over sensorimotor cortex and the other over posterior parietal cortex, with homologous foci in opposite hemispheres arising from oscillations 180 degrees out of phase. These findings demonstrate temporal isomorphism at a neural level between overt and imagined movements and illustrate a new approach to studying covert actions.